title: Development and characterization of lyophilized diazepam-loaded polymeric micelles.
abstract: Polymeric micelles were studied as delivery carriers of diazepam, a practically insoluble drug in water, for rectal administration. The diazepam-loaded polymeric micelles were developed by using poloxamer 407 (P407), poloxamer 188, and D-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS). Among the used polymers, TPGS resulted in polymeric micelles with good characteristics for encapsulation of diazepam which had the small particle size of 8-12 nm and narrow size distribution (PI 0.053-0.275). Additionally, 7.5% w/v of TPGS could entirely entrap the desired concentration of diazepam (5 mg/mL). To improve the physical stability upon lyophilization, an addition of P407 of 1% w/v prevented aggregation, increased physical stability, and maintained chemical stability of the lyophilized powders of diazepam-loaded polymeric micelles for 3 months storage at 4°C. The rate and amount of diazepam release from TPGS polymeric micelles mainly depended on the concentration of TPGS. The release data were fitted to Higuchi's model suggesting that the drug release mechanism was controlled by Fickian diffusion. In conclusion, 10% w/v TPGS and 1% w/v P407 were the optimum formulation of lyophilized diazepam-loaded polymeric micelles.
authors.affiliation: Excellent Center of Innovative Drug Delivery and Nanomedicine, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayutthaya Road, Rajthevi, Bangkok, 10400, Thailand, jiraphong.suk@mahidol.ac.th.
authors.forename: Jiraphong
authors.initials: J
authors.lastname: Suksiriworapong
authors.forename: Tanaporn
authors.initials: T
authors.lastname: Rungvimolsin
authors.forename: Atitaya
authors.initials: A
authors.lastname: A-gomol
authors.forename: Varaporn Buraphacheep
authors.initials: VB
authors.lastname: Junyaprasert
authors.forename: Doungdaw
authors.initials: D
authors.lastname: Chantasart
mesh_terms: D003975:Diazepam / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D004355:Drug Stability; D005612:Freeze Drying / Q000379:methods; D008823:Micelles; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011208:Powders / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D011208:Powders; D020442:Poloxamer; D011092:Polyethylene Glycols; D003975:Diazepam